The present invention relates to a method and composition for treating equine anhidrosis.
Equine anhidrosis, first reported in British thoroughbreds taken to tropical colonies early in this century, is also known as "nonsweating", "dry-coat syndrome", "blowing" or "puff disease" and is manifested by ineffective sweating in response to appropriate stimuli. Sweat evaporation is the primary cooling mechanism for horses when the ambient temperature exceeds the body temperature. Anhidrotic horses have compromised thermoregulatory function and are in great danger of hyperthermia. Normal equine rectal temperature is about 99.5-101.5.degree. F.; if asked to perform at extremely high ambient temperatures, anhidrotic horses have been known to achieve rectal temperatures of 108.degree. F. and may collapse and die if raced. Providing shade or decreasing activity gives these horses minimal relief.
Anhidrosis appears to be precipitated by heat stress in humid environments in horses that have perhaps never previously experienced such conditions. Owners and veterinarians report that over a period of weeks or months, affected horses first show either profuse or delayed sweating and then gradually lose the ability to sweat altogether. Surveys in Florida revealed that anhidrosis can affect horses of all ages, breeds, colors, and affects both native horses and animals undergoing acclimatization. Anhidrosis is equally prevalent in horses at all levels of exercise, from idle pleasure horses to racehorses.
Clinical features of anhidrotic horses and hypohidrotic (deficient perspiration) horses include rapid breathing (tachypnea), the most common sign reported, fatigue and loss of hair (alopecia), especially of the face. Some animals may have a decreased appetite or decreased water consumption and poor performance. Secondary signs include changes in the proteinaceous secretion along with sweat which leads to dull hair coat, hair loss, scales and pruritus. Residual sweat areas include the crest, the neck, brisket and perineum.
The pathogenesis of anhidrosis is unknown. The lack of sweating could be due to a number of possible flaws in a complex sequence of events from central nervous stimulation ("CNS") through sweat stimulation and secretion, to delivery of sweat to the skin surface. The inability to produce or deliver sweat in response to the stimulus of tropical heat may include: (1) changes in gland stimulation either due to not enough central stimulus from CNS or an interruption in the neural stimulation; or (2) changes in gland or duct function, due to impaired gland response or changes in the secretory process, which impairs delivery of sweat to the skin surface; or (3) metabolic derangement of fluid, electrolyte losses, or an endocrine disturbance.
Studies of the ultrastructure of the sweat gland of such horses indicate that the condition, induced by continuous climatic stress, results from a gradual failure of the mechanism of sweat production and culminates in secretory, or sweat gland, cell degeneration. As reported in Jenkinson et al., Effects of Season and Lower Ambient Temperature on the Structure of the Sweat Glands in Anhidrotic Horses, Equine Vet.J (1989), 21(1), 59-65, histologically, the secretory cells become thin, in some cases less than 50% of normal size. In addition, the thinner cells generally contain few cytoplasmic granules and often contain large lysosomes. Removal of the thermal stress under controlled and/or natural environment has resulted in restoration of the activity of sweat glands on most anhidrotic horses studied. Early studies of anhidrosis demonstrated that the secretory failure is associated with a progressive reduction in the response of the glands to catecholamines.
Sweat glands have been classically divided into the categories eccrine and apocrine, on the basis of mechanism of secretion. The sweat glands in the horse are associated with hair follicles and have been classified as apocrine. Involvement of myoepithelial contraction in extrusion of sweat seems to vary among species, but sweat secretion is known to be continuous in cattle and horses.
Both apocrine and eccrine sweat glands are under control of the sympathetic nervous system. Pharmacologic studies strongly suggest the apocrine glands are controlled by the adrenergic sympathetic system, characterized by nerve fiber endings which secrete the synaptic transmitter substance norepinephrine, also known as noradrenaline.
Experimentally, sustained generalized sweating can be stimulated in the horse by intravenous administration of epinephrine, or localized by intradermal injection of epinephrine. Equine sweat glands respond most vigorously to beta-2-adrenergic stimulation. Sweating can be suppressed by a beta-adrenergic blocker (propanolol) but not by a beta-1 antagonist (metoprolol) when followed by epinephrine administration, which supports this observation. Beta-2-agonist (terbutaline, clenbutarol, etc.) are safely used as sudorific agents to test anhidrosis.
Hormonal studies have not been conclusive. Base line levels of thyroid hormone appear to be normal in anhidrotic horses. Circulating epinephrine concentrations are higher in anhidrotic than in normal horses, which may be of major significance in determining the pathogenesis of the disease.
Anhidrotic horses have been treated in the past with sodium chloride, iodine, potassium, and thyroid hormones. However, such treatments have not generally proven useful. The present knowledge about equine anhidrosis thus fails to include an effective method and composition for treating the affliction.